The β-elimination route to stereodefined γ-alkylidenebutenolides

gamma -Alkylidenebutenolides are biologically significant compounds and comprise compounds as structurally and functionally diverse as the inhibitor dihydroxerulin (Z-61, Scheme 16) of cholesterol biosynthesis or the carotinoid peridinin (Z-18a, Scheme 5) which plays a dominant role in marine photosynthesis. For the stereo-controlled obtention of gamma -alkylidenebutenolides Z-2 or E-2 with or without alkyl substituents at C-alpha or C-beta, a general strategy has been developed (Scheme 1). The key step of this strategy is the stereospecific anti-elimination of water from diastereopure gamma-(alpha -hydroxyalkyl)butenolides lk-1 or ul-1-be they racemic or enantiopure (lk = like, ul = unlike: gamma-(alpha -hydroxyalkyl)butenolides lk-1 give gamma -alkylidenebutenolides Z-2, while gamma-(alpha -hydroxyalkyl)butenolides ul-1 furnish the isomeric gamma -alkylidenebutenolides E-2. As dehydrating agents we used mixtures of triflic anhydride and pyridine or of diethyl azodicarboxylate and triphenylphosphine. Previous beta -eliminations providing gamma -alkylidenebutenolides exhibited in general little stereoselectivity and no stereospecifity at all (exception: Scheme 10), irrespective of whether this beta -elimination was performed separately or took place in situ.